tbuckley/cabot-search huggingface dataset:
Microbial metabolite butyrate promotes anti-PD-1 antitumor efficacy by modulating T cell receptor signaling of cytotoxic CD8 T cell
Authors: Xinhai Zhu, Ke Li, Guichao Liu, Ruan Wu, Yan Zhang, Siying Wang, Meng Xu, Ligong Lu, Peng Li
Journal: Gut Microbes (2023)

Recent studies have demonstrated that the antitumor immunity of immune cells can be modulated by gut microbiota and their metabolites. However, the underlying mechanisms remain unclear. Here, we showed that the serum butyric acid level is positively correlated with the expression of programmed cell death-1 (PD-1) on circulating CD8+ and Vγ9 Vδ2 (Vδ2+) T cells in patients with non-small cell lung cancer (NSCLC). Responder NSCLC patients exhibited higher levels of serum acetic acid, propionic acid, and butyric acid than non-responders. Depletion of the gut microbiota reduces butyrate levels in both feces and serum in tumor-bearing mice. Mechanistically, butyrate increased histone 3 lysine 27 acetylation (H3K27ac) at the promoter region of Pdcd1 and Cd28 in human CD8+ T cells, thereby promoting the expression of PD-1/CD28 and enhancing the efficacy of anti-PD-1 therapy. Butyrate supplementation promotes the expression of antitumor cytokines in cytotoxic CD8+ T cells by modulating the T-cell receptor (TCR) signaling pathway. Collectively, our findings reveal that the metabolite butyrate of the gut microbiota facilitates the efficacy of anti-PD-1 immunotherapy by modulating TCR signaling of cytotoxic CD8 T cells, and is a highly promising therapeutic biomarker for enhancing antitumor immunity.
Portrayal of Women as Physicians in Movies, 1990-2020
Authors: Bismarck C. Odei, Sofia Herrera, Christina Huang, Kent A. Griffith, Junu Bae, Alejandra Zaleta Lastra, Reshma Jagsi
Journal: JAMA Internal Medicine (2023)

This cross-sectional study quantifies the portrayal of women as physicians in US movies over the past 3 decades.
Prediction Model for Early-Stage Pancreatic Cancer Using Routinely Measured Blood Biomarkers
Authors: Lenka N. C. Boyd, Mahsoem Ali, Annalisa Comandatore, Ingrid Garajova, Laura Kam, Jisce R. Puik, Stephanie M. Fraga Rodrigues, Laura L. Meijer, Tessa Y. S. Le Large, Marc G. Besselink, Luca Morelli, Adam Frampton, Hanneke W. M. van Laarhoven, Elisa Giovannetti, Geert Kazemier
Journal: JAMA Network Open (2023)

Accurate risk prediction models using routinely measured biomarkers-eg, carbohydrate antigen 19-9 (CA19-9) and bilirubin serum levels-for pancreatic cancer could facilitate early detection of pancreatic cancer and prevent potentially unnecessary diagnostic tests for patients at low risk. An externally validated model using CA19-9 and bilirubin serum levels in a larger cohort of patients with pancreatic cancer or benign periampullary diseases is needed.To assess the discrimination, calibration, and clinical utility of a prediction model using readily available blood biomarkers (carbohydrate antigen 19-9 [CA19-9] and bilirubin) to distinguish early-stage pancreatic cancer from benign periampullary diseases.This diagnostic study used data from 4 academic hospitals in Italy, the Netherlands, and the UK on adult patients with pancreatic cancer or benign periampullary disease treated from 2014 to 2022. Analyses were conducted from September 2022 to February 2023.Serum levels of CA19-9 and bilirubin from samples collected at diagnosis and before start of any medical intervention.Discrimination (measured by the area under the curve [AUC]), calibration, and clinical utility of the prediction model and the biomarkers, separately.The study sample comprised 249 patients in the development cohort (mean [SD] age at diagnosis, 67 [11] years; 112 [45%] female individuals), and 296 patients in the validation cohort (mean [SD] age at diagnosis, 68 [12] years; 157 [53%] female individuals). At external validation, the prediction model showed an AUC of 0.89 (95% CI, 0.84-0.93) for early-stage pancreatic cancer vs benign periampullary diseases, and outperformed CA19-9 (difference in AUC [ΔAUC], 0.10; 95% CI, 0.06-0.14; P < .001) and bilirubin (∆AUC, 0.07; 95% CI, 0.02-0.12; P = .004). In the subset of patients without elevated tumor marker levels (CA19-9 <37 U/mL), the model showed an AUC of 0.84 (95% CI, 0.77-0.92). At a risk threshold of 30%, decision curve analysis indicated that performing biopsies based on the prediction model was equivalent to reducing the biopsy procedure rate by 6% (95% CI, 1%-11%), without missing early-stage pancreatic cancer in patients.In this diagnostic study of patients with pancreatic cancer or benign periampullary diseases, an easily applicable risk score showed high accuracy for distinguishing early-stage pancreatic cancer from benign periampullary diseases. This model could be used to assess the added diagnostic and clinical value of novel biomarkers and prevent potentially unnecessary invasive diagnostic procedures for patients at low risk.
The Obesity Paradox in Patients in Need of Extracorporeal Membrane Oxygenation
Authors: Peter Pickkers
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

The Obesity Paradox in Patients in Need of Extracorporeal Membrane OxygenationAlthough the coronavirus disease (COVID-19) pandemic was overwhelming, let us not forget that, in recent decades, another more slumbering pandemic was also raging: the obesity pandemic.The COVID-19 pandemic highlighted the interplay among obesity, adult respiratory distress syndrome (ARDS), and the need for ventilatory support.Early during the COVID-19 pandemic, obesity was recognized as an important risk factor for susceptibility to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as well as an unfavorable disease course of COVID-19.Consequently, COVID-19 patients with a higher body mass index (BMI) were more likely to need intensive care treatment.Intriguingly, when admitted to the ICU, the prognosis of obese patients was not worse (1) or was even better (2) than the prognosis of patients of normal weight.
Figure Label Correction
Journal: JAMA (2023)

César Caraballo, MD; Daisy S. Massey, BA; Chima D. Ndumele, PhD; Trent Haywood, MD, JD; Shayaan Kaleem; Terris King, BS, MS, ScD; Yuntian Liu, MPH; Yuan Lu, ScD; Marcella Nunez-Smith, MD, MHS; Herman A. Taylor, MD, MPH; Karol E. Watson, MD, PhD; Jeph Herrin, PhD; Clyde W. Yancy, MD, MSc; Jeremy Samuel Faust, MD, MS; Harlan M. Krumholz, MD, SM
Assessing the Clinical Utility of Liquid Biopsies Across 5 Potential Indications From Therapy Selection to Population Screening
Authors: David J. Carr, H. Gilbert Welch
Journal: JAMA Internal Medicine (2023)

There has been great enthusiasm for the emerging technology of molecular-based tests to detect and quantify tumor DNA circulating in the bloodstream, colloquially known as a liquid biopsy. However, less attention has been given to how their clinical utility depends on the indication for testing, which includes a range of clinical situations, each presenting unique challenges.Five indications for circulating tumor DNA (ctDNA) blood testing were considered. (1) For therapy selection, ctDNA tests can identify genetic alterations in patients with cancer amenable to targeted therapy, but most patients do not have a targetable alteration. (2) For response to therapy, the absence of residual tumor DNA following cancer surgery could reduce the use of adjuvant chemotherapy, but it is unclear that this will happen in practice. (3) For disease surveillance following cancer treatment, ctDNA tests may well detect cancer recurrence before symptoms appear, yet earlier intervention may have no effect on mortality. (4) For diagnosis of suspected cancer, ctDNA tests are able to identify some symptomatic cancers, but how they add to the conventional diagnostic evaluation is unknown. (5) For screening for cancer, multicancer tests can detect many types of cancer, but their low sensitivity for early-stage tumors raises questions as to whether screening can help patients live longer or live better.Circulating tumor DNA tests are being promoted for multiple indications. Numerous studies are ongoing, but randomized clinical trials of their effect on patient-centered outcomes are rare. While these tests have the potential to improve care in selected indications, this must be proven, as they will add cost, complexity, and unintended adverse effects for patients.
Muvalaplin, an Oral Small Molecule Inhibitor of Lipoprotein(a) Formation
Authors: Stephen J. Nicholls, Steven E. Nissen, Cynthia Fleming, Shweta Urva, Jeffrey Suico, Paul H. Berg, Helle Linnebjerg, Giacomo Ruotolo, P. Kellie Turner, Laura F. Michael
Journal: JAMA (2023)

Lipoprotein(a) (Lp[a]) is associated with atherosclerotic disease and aortic stenosis. Lp(a) forms by bonding between apolipoprotein(a) (apo[a]) and apo B100. Muvalaplin is an orally administered small molecule that inhibits Lp(a) formation by blocking the apo(a)-apo B100 interaction while avoiding interaction with a homologous protein, plasminogen.
Estimated Prevalence of Depressive Disorders in Children From 2004 to 2019
Authors: Michael J. Spoelma, Gemma L. Sicouri, Deanna A. Francis, Annabel D. Songco, Emily K. Daniel, Jennifer L. Hudson
Journal: JAMA Pediatrics (2023)

Depression during childhood (ie, age <13 years) poses a major health burden. Recent changes in environmental and lifestyle factors may increase children's risk of mental health problems. This has been reported for anxiety disorders, but it is unclear whether this occurs for depressive disorders.To provide prevalence estimates for the depressive disorders (ie, major depressive disorder [MDD], dysthymia, disruptive mood dysregulation disorder [DMDD], and overall) in children, and whether they have changed over time.The MEDLINE, PsycINFO, Embase, Scopus, and Web of Science databases were searched using terms related to depressive disorders, children, and prevalence. This was supplemented by a systematic gray literature search.Studies were required to provide population prevalence estimates of depressive disorder diagnoses (according to an established taxonomy and standardized interviews) for children younger than 13 years, information about participants' year of birth, and be published in English.Data extraction was compliant with the Meta-Analysis of Observational Studies in Epidemiology guidelines. A total of 12 985 nonduplicate records were retrieved, and 154 full texts were reviewed. Data were analyzed from 2004 (the upper limit of a previous review) to May 27, 2023. Multiple proportional random-effects meta-analytic and mixed-effects meta-regression models were fit.Pooled prevalence rates of depressive disorders, prevalence rate differences between males vs females and high-income countries (HICs) vs low-and middle-income countries (LMICs), and moderating effects of time or birth cohort.A total of 41 studies were found to meet the inclusion criteria. Pooled prevalence estimates were obtained for 1.07% (95% CI, 0.62%-1.63%) for depressive disorders overall, 0.71% (95% CI, 0.48%-0.99%) for MDD, 0.30% (95% CI, 0.08%-0.62%) for dysthymia, and 1.60% (95% CI, 0.28%-3.90%) for DMDD. The meta-regressions found no significant evidence of an association with birth cohort, and prevalence rates did not differ significantly between males and females or between HICs and LMICs. There was a low risk of bias overall, except for DMDD, which was hindered by a lack of studies.In this systematic review and meta-analysis, depression in children was uncommon and did not increase substantially between 2004 and 2019. Future epidemiologic studies using standardized interviews will be necessary to determine whether this trend will continue into and beyond the COVID-19 pandemic.
Testing Whether Cancer Screening Saves Lives
Authors: H. Gilbert Welch, Tanujit Dey
Journal: JAMA Internal Medicine (2023)

Importance Cancer screening is often promoted as a means to save lives. The question of whether cancer screening truly saves lives is becoming increasingly relevant given the growing enthusiasm for multicancer detection blood tests (ie, liquid biopsies). It is possible in randomized clinical trials for screening to reduce deaths due to the targeted cancer without reducing deaths due to all causes. To explore the feasibility of powering studies for cancer-specific vs all-cause mortality, a series of sample size calculations was performed for selected cancers (breast, colorectal, liver, pancreas, and prostate) and for all cancers combined. Observations Randomized clinical trials of screening for an individual cancer typically require 100 000 or more participants to test its effect on cancer-specific mortality. Testing all-cause mortality requires trials of more than a million participants. However, the sample size requirements change markedly when considering a randomized clinical trial of screening for all cancers, as is envisioned when using multicancer detection blood tests. In this setting, the question of whether cancer screening reduces all-cause mortality can be reasonably addressed in a trial of fewer than 100 000 participants. Conclusions and Relevance It is not feasible to test all-cause mortality when screening for an individual cancer. However, it is feasible to test all-cause mortality for multicancer screening because cancer deaths are such a large component of deaths in general. Observational data on the effects of cancer screening are misleading. Multicancer screening would entail tremendous costs and potentially substantial harms. For these reasons, a randomized clinical trial is mandatory not only to learn if multicancer screening saves lives, but also to learn how frequently it causes harm.
The Need for Randomized Clinical Trials Demonstrating Reduction in All-Cause Mortality With Blood Tests for Cancer Screening
Authors: Sanket S. Dhruva, Rebecca Smith-Bindman, Rita F. Redberg
Journal: JAMA Internal Medicine (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Effect of Mavacamten on Chinese Patients With Symptomatic Obstructive Hypertrophic Cardiomyopathy
Authors: Zhuang Tian, Liwen Li, Xiaoyan Li, Jian’an Wang, Qing Zhang, Zhanquan Li, Daoquan Peng, Ping Yang, Wei Ma, Fang Wang, Wei Jin, Xiang Cheng, Jing Sun, Yiqun Fu, Cheng Lyu, Shuyang Zhang
Journal: JAMA Cardiology (2023)

Mavacamten has shown clinical benefits in global studies for patients with obstructive hypertrophic cardiomyopathy (oHCM), but evidence in the Asian population is lacking.
Is It Time to Reconsider the Diagnostic Construct Validity of Depressive Disorders for Young Children?
Authors: Sheri Madigan, Daphne J. Korczak
Journal: JAMA Pediatrics (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Career Plans of Internal Medicine Residents From 2019 to 2021
Authors: Neha Paralkar, Nancy LaVine, Saoirse Ryan, Rosemarie Conigliaro, Jason Ehrlich, Aisha Khan, Lauren Block
Journal: JAMA Internal Medicine (2023)

This survey study examines career choices of internal medicine residents from 2019 to 2021 and compares them with findings from a decade earlier.
Phase <scp>II</scp> study of cladribine, idarubicin, and <scp>ara‐C</scp> (<scp>CLIA</scp>) with or without sorafenib as initial therapy for patients with acute myeloid leukemia
Authors: Tapan M. Kadia, Farhad Ravandi, Matteo Molica, Alex Bataller, Gautam Borthakur, Naval Daver, Elias Jabbour, Courtney D. DiNardo, Naveen Pemmaraju, Nitin Jain, Alessandra Ferrajoli, Musa Ylimaz, Prithviraj Bose, Rebecca Slack Tidwell, Kayleigh R. Marx, Caitlin R. Rausch, Rashmi Kanagal‐Shamanna, Sa Wang, Rabiul Islam, Richard Champlin, Elizabeth Shpall, Marina Konopleva, Guillermo Garcia‐Manero, Hagop Kantarjian
Journal: American Journal of Hematology (2023)

The addition of cladribine, or sorafenib to standard chemotherapy have each demonstrated improved survival in patients with newly-diagnosed acute myeloid leukemia (AML). We studied the combination of cladribine, idarubicin, and intermediate-dose cytarabine (CLIA) in patients ≤65 years of age with newly diagnosed AML, fit to receive intensive therapy. Cladribine (5 mg/m2) IV was administered on days (D)1-5, cytarabine (1 g/m2) on D1-5, and idarubicin (10 mg/m2) on D1-3. Sorafenib was added to the CLIA backbone for patients with FLT3-ITD mutated AML. 80 patients were enrolled: 65 with newly diagnosed AML and 15 with AML arising from previously treated MDS (ts-AML). The median age was 55 years (range, 21-65). CR + CRi was 83% (54/65) and 27% in the untreated and ts-AML cohorts, respectively; 74% and 75% of responding patients, respectively, had undetectable measurable residual disease (MRD). Among patients with FLT3-ITD mutated AML receiving CLIA+sorafenib, the CR + CRi rate was 95%, with 81% negative for MRD. With a median follow-up of 76 months, the 2- and 4-year OS of 57% and 50% compared to 20%, and 13% for ts-AML, respectively. Patients treated with CLIA+sorafenib had 2- and 5-year OS rates of 63% and 59%, respectively. The most common Grade ≥3 adverse events were infection/fever, elevated bilirubin, rash, and nausea. CLIA was safe and effective in young, fit patients with newly diagnosed AML with inferior outcomes among patients with ts-AML. The addition of sorafenib to CLIA in FLT3-ITD mutated AML resulted in high rates of durable remission and excellent long-term survival.
Prognostic value of three iron deficiency definitions in patients with advanced heart failure
Authors: Charikleia Papadopoulou, Johannes Reinhold, Nicolai Grüner‐Hegge, Anna Kydd, Sai Bhagra, K. Jayan Parameshwar, Clive Lewis, Luis Martinez, Stephen J. Pettit
Journal: European Journal of Heart Failure (2023)

There is uncertainty about the definition of iron deficiency (ID) and the association between ID and prognosis in patients with advanced heart failure. We evaluated three definitions of ID in patients referred for heart transplantation.Consecutive patients assessed for heart transplantation at a single UK centre between January 2010 and May 2022 were included. ID was defined as (1) serum ferritin concentration of <100 ng/ml, or 100-299 ng/ml with transferrin saturation <20% (guideline definition), (2) serum iron concentration ≤13 μmol/L, or (3) transferrin saturation <20%. The primary outcome measure was a composite of all-cause mortality, urgent heart transplantation or need for mechanical circulatory support. Overall, 801 patients were included, and the prevalence of ID was 39-55% depending on the definition used. ID, defined by either serum iron or transferrin saturation, was an independent predictor of the primary outcome measure (hazard ratio [HR] 1.532, 95% confidence interval [CI] 1.264-1.944, and HR 1.595, 95% CI 1.323-2.033, respectively), but the same association was not seen with the guideline definition of ID (HR 1.085, 95% CI 0.8827-1.333). These findings were robust in multivariable Cox regression analysis. ID, by all definitions, was associated with lower 6-min walk distance, lower peak oxygen consumption, higher intra-cardiac filling pressures and lower cardiac output.Iron deficiency, when defined by serum iron concentration or transferrin saturation, was associated with increased frequency of adverse clinical outcomes in patients with advanced heart failure. The same association was not seen with guideline definition of ID.
All-Cause Mortality and Cardiovascular and Microvascular Diseases in Latent Autoimmune Diabetes in Adults
Authors: Yuxia Wei, Katharina Herzog, Emma Ahlqvist, Tomas Andersson, Thomas Nyström, Yiqiang Zhan, Tiinamaija Tuomi, Sofia Carlsson
Journal: Diabetes Care (2023)

OBJECTIVE Latent autoimmune diabetes in adults (LADA) is a heterogenous, slowly progressing autoimmune diabetes. We aim to contribute new knowledge on the long-term prognosis of LADA with varying degrees of autoimmunity by comparing it to type 2 diabetes and adult-onset type 1 diabetes. RESEARCH DESIGN AND METHODS This Swedish population-based study included newly diagnosed LADA (n = 550, stratified into LADAlow and LADAhigh by median autoimmunity level), type 2 diabetes (n = 2,001), adult-onset type 1 diabetes (n = 1,573), and control subjects without diabetes (n = 2,355) in 2007–2019. Register linkages provided information on all-cause mortality, cardiovascular diseases (CVDs), diabetic retinopathy, nephropathy, and clinical characteristics during follow-up. RESULTS Mortality was higher in LADA (hazard ratio [HR] 1.44; 95% CI 1.03, 2.02), type 1 (2.31 [1.75, 3.05]), and type 2 diabetes (1.31 [1.03, 1.67]) than in control subjects. CVD incidence was elevated in LADAhigh (HR 1.67; 95% CI 1.04, 2.69) and type 2 diabetes (1.53 [1.17, 2.00]), but not in LADAlow or type 1 diabetes. Incidence of retinopathy but not nephropathy was higher in LADA (HR 2.25; 95% CI 1.64, 3.09), including LADAhigh and LADAlow than in type 2 diabetes (unavailable in type 1 diabetes). More favorable blood pressure and lipid profiles, but higher HbA1c levels, were seen in LADA than type 2 diabetes at baseline and throughout follow-up, especially in LADAhigh, which resembled type 1 diabetes in this respect. CONCLUSIONS Despite having fewer metabolic risk factors than type 2 diabetes, LADA has equal to higher risks of death, CVD, and retinopathy. Poorer glycemic control, particularly in LADAhigh, highlights the need for improved LADA management.
Medications for Opioid Use Disorder During the Prenatal Period and Infant Outcomes
Authors: Mir M. Ali, Kristina D. West, Rachel Mosher Henke, Michael A. Head, Stephen W. Patrick
Journal: JAMA Pediatrics (2023)

This cross-sectional study explores the association between mothers’ receipt of opioid use disorder treatment during pregnancy and their infants’ health services use in the first year of life.